Spiriva Handihaler

  • Asthma/COPD

Spiriva Handihaler Generic Name & Formulations

General Description

Tiotropium (as bromide monohydrate) 18mcg/cap; dry pwd in caps for oral inhalation; with inhaler device.

Pharmacological Class

Long-acting anticholinergic.

See Also

How Supplied

HandiHaler (caps w. inh device)—5, 30, 90; Respimat (cartridge w. inh device)—4g (60 inh)

How Supplied

Spiriva Handihaler consists of Spiriva capsules and the Handihaler device. Spiriva capsules contain 18 mcg of tiotropium and are light green, with the Boehringer Ingelheim company logo on the Spiriva capsule cap and TI 01 on the Spiriva capsule body, or vice versa. 

The Handihaler device is gray colored with a green piercing button. It is imprinted with Spiriva Handihaler (tiotropium bromide inhalation powder), the Boehringer Ingelheim company logo. It is also imprinted to indicate that Spiriva capsules should not be stored in the Handihaler device and that the Handihaler device is only to be used with Spiriva capsules.

Spiriva capsules are packaged in an aluminum/aluminum blister card and joined along a perforated-cut line. Spiriva capsules should always be stored in the blister and only removed immediately before use. The drug should be used immediately after the packaging over an individual Spiriva capsule is opened. 

The following packages are available:  

  • carton containing 5 Spiriva capsules (1 unit-dose blister card) and 1 Handihaler inhalation device (institutional pack)  

  • carton containing 30 Spiriva capsules (3 unit-dose blister cards) and 1 Handihaler inhalation device  

  • carton containing 90 Spiriva capsules (9 unit-dose blister cards) and 1 Handihaler inhalation device 


Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

The Spiriva capsules should not be exposed to extreme temperature or moisture. Do not store Spiriva capsules in the Handihaler device. 

Generic Availability


Spiriva Handihaler Indications


Long-term maintenance treatment of bronchospasm due to COPD, including chronic bronchitis and emphysema. To reduce exacerbations of COPD.

Spiriva Handihaler Dosage and Administration


2 inh of one capsule contents (18mcg) once daily, using HandiHaler inhalation device. Max: 2 inh/24hrs. Do not swallow caps.


Not established.

Spiriva Handihaler Contraindications


Allergy to ipratropium.

Spiriva Handihaler Boxed Warnings

Not Applicable

Spiriva Handihaler Warnings/Precautions


Not for the relief of acute symptoms. Discontinue if immediate hypersensitivity reactions (eg, angioedema) or paradoxical bronchospasm occurs; consider alternative therapy. Monitor for signs/symptoms of worsening narrow-angle glaucoma or worsening urinary retention (esp. GI or GU obstruction). Moderate-to-severe renal impairment; monitor for anticholinergic effects. Allergy to atropine or its derivatives; monitor. HandiHaler: avoid getting powder into eyes; or allergy to milk proteins. Pregnancy. Nursing mothers.


Not for Acute Use

  • Spiriva Handihaler is intended as a once-daily maintenance treatment for COPD and should not be used for relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. 

Immediate Hypersensitivity Reactions 

  • Spiriva Handihaler may cause immediate hypersensitivity reactions, including urticaria, angioedema (including swelling of the lips, tongue, or throat), rash, bronchospasm, anaphylaxis, or itching.

  • Discontinue therapy immediately and consider alternative treatments if hypersensitivity reactions occur.

  • Monitor closely patients with a history of hypersensitivity reactions to atropine or its derivatives. Use caution in patients with severe hypersensitivity to milk proteins.

Paradoxical Bronchospasm

  • May cause paradoxical bronchospasm.

  • Treat immediately with an inhaled short-acting beta1-agonist (e.g., albuterol) if paradoxical bronchospasm occurs; discontinue treatment with Spiriva Handihaler and consider other treatments.

Worsening of Narrow-Angle Glaucoma

  • Use caution in patients with narrow-angle glaucoma.

  • Be alert for signs and symptoms of acute narrow-angle glaucoma (e.g., eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema).

Worsening of Urinary Retention

  • Use caution in patients with narrow-angle glaucoma.

  • Be alert for signs and symptoms of urinary retention (e.g., difficulty passing urine, painful urination), especially in patients with prostatic hyperplasia or bladder-neck obstruction.

Renal Impairment 

  • Patients with moderate to severe renal impairment (CrCl <60 mL/min) treated with Spiriva Handihaler should be monitored closely for anticholinergic side effects.

Pregnancy Considerations

Risk Summary 

  • Insufficient data to inform a drug-associated risk of adverse pregnancy-related outcomes.

Nursing Mother Considerations

Risk Summary

  • No data on the presence of tiotropium in human milk, the effects on the breastfed infant, or the effects on milk production.

  • The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Spiriva Handihaler and any potential adverse effects on the breastfed child from Spiriva Handihaler or from the underlying maternal condition. 

Pediatric Considerations

The safety and effectiveness of Spiriva Handihaler in pediatric patients have not been established.

Geriatric Considerations

Based on available data, no dosage adjustment in geriatric patients is warranted.

Renal Impairment Considerations

Monitor closely in patients with moderate to severe renal impairment (creatinine clearance of <60 mL/min) for anticholinergic side effects.

Hepatic Impairment Considerations

The effects of hepatic impairment on the pharmacokinetics of tiotropium were not studied.

Spiriva Handihaler Pharmacokinetics


Following dry powder inhalation by young healthy volunteers, the absolute bioavailability of 19.5% suggests that the fraction reaching the lung is highly bioavailable. Oral solutions of tiotropium have an absolute bioavailability of 2-3%. Food is not expected to influence the absorption of tiotropium. Maximum tiotropium plasma concentrations were observed 7 minutes after inhalation.


Tiotropium is 72% bound to plasma protein and had a volume of distribution of 32 L/kg after intravenous administration to young healthy volunteers. Local concentrations in the lung are not known, but the mode of administration suggests substantially higher concentrations in the lung. Studies in rats have shown that tiotropium does not readily penetrate the blood-brain barrier.


In vitro experiments with human liver microsomes and human hepatocytes suggest that a fraction of the administered dose (74% of an intravenous dose is excreted unchanged in the urine, leaving 25% for metabolism) is metabolized by cytochrome P450-dependent oxidation and subsequent glutathione conjugation to a variety of Phase II metabolites.


The terminal half-life of tiotropium in COPD patients following once daily inhalation of 5 mcg tiotropium was approximately 25 hours. Total clearance was 880 mL/min after intravenous administration in young healthy volunteers. After chronic once-daily dry powder inhalation by COPD patients, pharmacokinetic steady state was reached by day 7 with no accumulation thereafter. 

Intravenously administered tiotropium bromide is mainly excreted unchanged in urine (74%). After dry powder inhalation to COPD patients at steady state, urinary excretion was 7% (1.3mcg) of the unchanged dose over 24 hours. The renal clearance of tiotropium exceeds the creatinine clearance, indicating secretion into the urine.

Spiriva Handihaler Interactions


Avoid other anticholinergics.

Spiriva Handihaler Adverse Reactions

Adverse Reactions

Upper respiratory tract infection, dry mouth, sinusitis, pharyngitis, bronchitis, cough, headache, non-specific chest pain, UTI, dyspepsia, rhinitis, other anticholinergic effects (eg, urinary retention, constipation, dysuria, tachycardia, blurred vision, glaucoma); paradoxical bronchospasm.

Spiriva Handihaler Clinical Trials

Clinical Trials

The efficacy of Spiriva Handihaler was evaluated in six phase 3 studies which included 2663 patients with COPD (1308 receiving Spiriva Handihaler): two 1-year, placebo-controlled studies, two 6-month, placebo-controlled studies and two 1-year, ipratropium-controlled studies. Eligible patients included a clinical diagnosis of COPD, were 40 years of age or older, had a history of smoking greater than 10 pack-years, had a forced expiratory volume in one second (FEV1) less than or equal to 60% or 65% of predicted, and a ratio of FEV1/FVC of less than or equal to 0.7. Patients received Spiriva Handihaler once-daily in the morning. Results showed that treatment with Spiriva Handihaler provided improvement in lung function (FEV1), with peak effect occurring within 3 hours following the first dose.

The efficacy of Spiriva Handihaler was also evaluated for exacerbations in 2 additional trials: a 6-month, randomized, double-blind, placebo-controlled, multicenter clinical trial of 1829 COPD patients in a US Veterans Affairs setting and a 4-year, randomized, double-blind, placebo-controlled, multicenter, clinical trial of 5992 COPD patients. Long-term effects on lung function and other outcomes, were also evaluated in the 4-year multicenter trial.


6-Month to 1-Year Effects on Lung Function

In the 1-year, placebo-controlled trials:

  • Mean improvement in FEV1 at 30 minutes was 0.13 liters (13%) with a peak improvement of 0.24 liters (24%) relative to baseline after the first dose (Day 1).

  • Mean peak improvement in FEV1, relative to baseline, was 0.28 to 0.31 liters (28% to 31%), after 1 week (Day 8) of once-daily treatment.

  • Improvement of lung function was maintained for 24 hours after a single dose and consistently maintained over the 1-year treatment period with no evidence of tolerance. 

In the two 6-month, placebo-controlled trials: (see full labeling for Figure 1 and 2)

  • Serial spirometric evaluations were performed throughout daytime hours in Trial A (12 hours) and limited to 3 hours in Trial B. The serial FEV1 values over 12 hours (Trial A) are displayed in Figure 1. These trials further support the improvement in pulmonary function (FEV1) with Spiriva Handihaler, which persisted over the spirometric observational period. Effectiveness was maintained for 24 hours after administration over the 6-month treatment period. 

  • Results of each of the 1-year ipratropium-controlled trials were similar to the results of the 1-year placebo-controlled trials. The results of one of these trials are shown in Figure 2.

In a randomized, placebo-controlled clinical study, the administration of Spiriva Handihaler in the morning or in the evening to 105 patients with COPD showed that bronchodilation was maintained throughout the 24-hour dosing interval compared with placebo. 

Throughout each week of the 1-year treatment period in the two placebo-controlled trials, treatment with Spiriva Handihaler had a reduced requirement for the use of rescue short-acting beta2-agonists. In 1 of the two 6 month studies, there was also a reduction in the use of rescue short-acting beta2-agonists with Spiriva Handihaler compared with placebo.


4-Year Effects on Lung Function: (see full labeling for Figure 3)

In a 4-year, randomized, double-blind, placebo-controlled, multicenter clinical trial, the long-term effects of Spiriva Handihaler were evaluated in 5992 COPD patients on disease progression (rate of decline in FEV1). Patients were allowed to use all respiratory medications (including short-acting and longacting beta-agonists, inhaled and systemic steroids, and theophyllines) other than inhaled anticholinergics. 

The trial included patients 40 to 88 years of age, 75% male, and 90% Caucasian with a diagnosis of COPD and a mean pre-bronchodilator FEV1 of 39% predicted (range = 9% to 76%) at study entry. There was no difference between the groups in either of the co-primary efficacy endpoints, yearly rate of decline in pre- and post-bronchodilator FEV1, as demonstrated by similar slopes of FEV1 decline over time. 

Spiriva Handihaler maintained improvements in trough (pre-dose) FEV1 (adjusted means over time: 87 to 103 mL) throughout the 4 years of the study.



The effect of Spiriva Handihaler on COPD exacerbations was evaluated in 2 clinical trials: a 4-year clinical trial described above and a 6-month clinical trial of 1829 COPD patients in a Veterans Affairs setting. 

In the 6-month trial, COPD exacerbations were defined as a complex of respiratory symptoms (increase or new onset) of more than 1 of the following: cough, sputum, wheezing, dyspnea, or chest tightness with a duration of at least 3 days requiring treatment with antibiotics, systemic steroids, or hospitalization. Patients were permitted to use respiratory medications (including short-acting and long-acting beta-agonists, inhaled and systemic steroids, and theophyllines) other than inhaled anticholinergics. The coprimary endpoints were the proportion of patients with COPD exacerbation and the proportion of patients with hospitalization due to COPD exacerbation. 

Results showed that treatment with Spiriva Handihaler significantly reduced the proportion of COPD patients who experienced exacerbations compared to placebo (27.9% vs. 32.3%, respectively; Odds Ratio (OR) (tiotropium/placebo) = 0.81; 95% CI, 0.66-0.99; P =.037). There was a lower proportion of patients treated with Spiriva Handihaler who were hospitalized due to COPD exacerbations compared to those treated with placebo, 7.0% vs. 9.5%, respectively (OR = 0.72; 95% CI, 0.51-1.01; P =.056). 

In the 4-year multicenter trial, exacerbations were evaluated as a secondary outcome and were defined as an increase or new onset of more than 1 of the following respiratory symptoms (cough, sputum, sputum purulence, wheezing, dyspnea) with a duration of 3 or more days requiring treatment with antibiotics and/or systemic (oral, intramuscular, or intravenous) steroids. Spiriva Handihaler significantly reduced the risk of an exacerbation by 14% (Hazard Ratio (HR) = 0.86; 95% CI, 0.81-0.91; P <.001) and reduced the risk of exacerbation-related hospitalization by 14% (HR = 0.86; 95% CI, 0.78-0.95; P <.002) compared to placebo. The median time to first exacerbation was delayed from 12.5 months (95% CI, 11.5-13.8) in the placebo group to 16.7 months (95% CI, 14.9-17.9) in the Spiriva Handihaler group. 


All-Cause Mortality

In the 4-year placebo-controlled lung-function trial described above, the effects of Spiriva Handihaler on all-cause mortality was assessed compared to placebo. There were no significant differences in all-cause mortality rates between Spiriva Handihaler and placebo. The all-cause mortality of Spiriva Handihaler was also compared to tiotropium inhalation spray 5 mcg (Spiriva Respimat 5 mcg) in an additional long-term, randomized, double-blind, double-dummy active-controlled study with an observation period up to 3 years. All-cause mortality was similar between Spiriva Handihaler and Spiriva Respimat. 

Spiriva Handihaler Note

Not Applicable

Spiriva Handihaler Patient Counseling

Patient Counseling

Not for Acute Use

  • Instruct patients that Spiriva Handihaler is a once-daily maintenance bronchodilator and should not be used for immediate relief of breathing problems (i.e., as a rescue medication).  

Immediate Hypersensitivity Reactions

  • Inform patients that anaphylaxis, angioedema (including swelling of the lips, tongue, or throat), urticaria, rash, bronchospasm, or itching, may occur after administration. Immediately discontinue treatment and consult a physician if any of these signs or symptoms develop. 

Paradoxical Bronchospasm

  • Inform patients that paradoxical bronchospasm can occur. Discontinue Spiriva Handihaler if paradoxical bronchospasm occurs.

Worsening of Narrow-Angle Glaucoma

  • Be alert for signs and symptoms of narrow-angle glaucoma (e.g., eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema). Consult a physician immediately should any of these signs and symptoms develop. 

  • Do not allow the powder to enter into the eyes as this may cause blurring of vision and pupil dilation. Since dizziness and blurred vision may occur with the use of Spiriva Handihaler, caution patients about engaging in activities such as driving a vehicle or operating appliances or machinery.

Worsening of Urinary Retention

  • Be alert for signs and symptoms of urinary retention (e.g., difficulty passing urine, painful urination). Consult a physician immediately should any of these signs or symptoms develop. 

Instructions for Administering Spiriva Handihaler

  • Instruct patients on how to correctly administer Spiriva capsules using the Handihaler device. Instruct patients that Spiriva capsules should only be administered via the Handihaler device and the Handihaler device should not be used for administering other medications. 

  • Remind patients that the contents of Spiriva capsules are for oral inhalation only and must not be swallowed. 

  • Store Spiriva capsules in sealed blisters and to remove only one Spiriva capsule immediately before use or its effectiveness may be reduced. Discard unused additional Spiriva capsules that are exposed to air (i.e., not intended for immediate use).